NM_001363540.2:c.37+50208A>G

Variant names:

• chr7-112155894-T-C
• rs2214432
• NM_001363540.2:c.37+50208A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363540.2(DOCK4):​c.37+50208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,116 control chromosomes in the GnomAD database, including 36,393 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36393 hom., cov: 33)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403
• Publications: 3 publications found

Genes affected

DOCK4 (HGNC:19192): (dedicator of cytokinesis 4) This gene is a member of the dedicator of cytokinesis (DOCK) family and encodes a protein with a DHR-1 (CZH-1) domain, a DHR-2 (CZH-2) domain and an SH3 domain. This membrane-associated, cytoplasmic protein functions as a guanine nucleotide exchange factor and is involved in regulation of adherens junctions between cells. Mutations in this gene have been associated with ovarian, prostate, glioma, and colorectal cancers. Alternatively spliced variants which encode different protein isoforms have been described, but only one has been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.37+50208A>G		intron_variant	Intron 1 of 52	ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.37+50208A>G		intron_variant	Intron 1 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.37+50208A>G		intron_variant	Intron 1 of 51	1		ENSP00000404179.1
DOCK4	ENST00000476846.5	n.293+50208A>G		intron_variant	Intron 1 of 22	5
DOCK4	ENST00000661654.1	n.306+50208A>G		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104716 AN: 151998 Hom.: 36371 Cov.: 33

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.665

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.689 AC: 104794 AN: 152116 Hom.: 36393 Cov.: 33 AF XY: 0.693 AC XY: 51545 AN XY: 74372

African (AFR) AF: 0.739 AC: 30653 AN: 41488

American (AMR) AF: 0.591 AC: 9023 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2319 AN: 3470

East Asian (EAS) AF: 0.853 AC: 4419 AN: 5178

South Asian (SAS) AF: 0.842 AC: 4060 AN: 4824

European-Finnish (FIN) AF: 0.706 AC: 7464 AN: 10568

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44629 AN: 67998

Other (OTH) AF: 0.669 AC: 1415 AN: 2116

Alfa AF: 0.665 Hom.: 103340

Bravo AF: 0.680

Asia WGS AF: 0.823 AC: 2864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.56
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2214432; hg19: chr7-111795949;